This project was aimed at exploring the possible presence of soluble immunoreglatory factors of tumor origin. It was found that the presence of at least four irradiated, cultured human tumor cell lines could stimulate the proliferation of human lymphocytes; the observed proliferative stimulation was due to secreted factors as activity was present in the serum-free tumor cell supernatant (PNAS 87:4058-62, 1990). In addition, this supernatant has now been demonstrated to inhibit the proliferation of three human leukemic cell lines concomitantly with induction of differentiation. Immunologic and proliferative assays using ELLISAs, neutralizing antibodies, and recombinant standards indicated nonidentity of at least one secreted factor with any previously characterized cytokine. A factor with unique biophysical and biochemical properties which has now been purified by a combination of ion exchange, gel filtration, and hydrophobic interaction chromatography is currently being sequenced. Identification of secreted factor(s) from tumor cells as a source of mitogenic activity for lymphocytes and myeloid differentiation induction supports the idea that the tumor immunoenvironment as recognized by immunocytes is defined by soluble mediators in addition to the well- studied cell-cell contact interactions.